This proposal is for a long-standing, comprehensive, multidisciplinary program to train cardiovascular scientists in mechanisms of disease, and means to develop novel diagnostic and therapeutic approaches to cardiovascular illnesses. It focuses on the use of cellular, molecular, pharmacologic, physiologic and bioengineering approaches. The range of scientific disciplines in the training plan includes: 1) myocyte signaling and cell death, 2) cardiac development and regeneration, 3) the role of the extrasarcomeric cytoskeleton in cardiomyopathy, and 4) cardiac bioengineering. The proposal aims to continue with 2 pre-doctoral and 6 post-doctoral positions each year. The pre-doctoral training positions will draw from some of the best of a group of excellent students in the University of California, San Diego (UCSD) Biomedical Sciences, Bioengineering, and Medical Scientist Training (MSTP) programs. The postdoctoral positions are drawn from a large pool of Ph.D. postdoctoral fellows at UCSD, a Physician-Scientist Training Program (PSTP) in the Department of Medicine, and select cardiology fellows who demonstrate a strong interest in pursuing a career in cardiovascular science. The program aims to groom the trainees in acquisition of the knowledge and skills necessary to become independent investigators in cardiovascular research. At least two years of training will be required of all postdoctoral trainees. The Faculty of the program are from the Departments of Medicine, Pharmacology, Anesthesiology, School of Pharmacy and Bioengineering at UCSD and draw from the resources of the School of Medicine, School of Engineering, the Institute of Engineering in Medicine, the Cardiac Biological Science and Engineering Center, the new Sulpizio Cardiovascular Center, the Skaggs School of Pharmacy and Pharmaceutical Sciences and the Department of Veterans Affairs Medical Center. The program has both didactic and laboratory experiences. Most trainees will be cross-trained in several disciplines. Thoughtful career guidance will be a component of all stages of the program. Importantly, the training program will be tailored to meet each individual's specific long-term goals, to equip them best for a successful future in academic medicine and research. 117 trainees have received support from this training program since its inception in 1978. Almost 50% now hold positions as academic faculty with several serving in or having served in leadership positions. Another 30% have scientific positions in the biotechnology industry. Over the last 10 years, 81% of former trainees have continued to actively publish original work in journals cited by PubMed. This proposal will facilitate the continued pattern of success that has been established over the years. (End of Abstract)